ClinVar Miner

Submissions for variant NM_001127898.4(CLCN5):c.1942C>T (p.His648Tyr)

gnomAD frequency: 0.00006  dbSNP: rs782515769
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003064484 SCV003442409 uncertain significance not provided 2024-10-29 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 578 of the CLCN5 protein (p.His578Tyr). This variant is present in population databases (rs782515769, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CLCN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 2138099). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CLCN5 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV003064485 SCV003708794 uncertain significance Inborn genetic diseases 2022-05-26 criteria provided, single submitter clinical testing The c.1732C>T (p.H578Y) alteration is located in exon 10 (coding exon 9) of the CLCN5 gene. This alteration results from a C to T substitution at nucleotide position 1732, causing the histidine (H) at amino acid position 578 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005045201 SCV005682721 uncertain significance Dent disease type 1; Hypophosphatemic rickets, X-linked recessive; X-linked recessive nephrolithiasis with renal failure; Proteinuria, low molecular weight, with hypercalciuria and nephrocalcinosis 2024-05-18 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.